Role of Tumor Necrosis Factor Alpha Induced Protein-8 Like-2 as a Biomarker of Parkinson's Disease

Document Type : Original Article

Authors

1 Department of Neurology, Faculty of Medicine, Beni-Suef University, Egypt

2 Department of Clinical Neurophysiology (Neuro-Diagnostic and Research Center), Faculty of Medicine, Beni-Suef University, Egypt

Abstract

Background and Aim: Neuroinflammation plays an early and prominent role in the pathology of Parkinson disease. Tumor necrosis factor alpha induced protein-8 like-2 (TIPE2) is a relatively new subtype of tumor necrosis factor which may play a role in pathogenesis of Parkinson disease. Our aim was to evaluate the role of serum level of TIPE2 as a risk factor for Parkinson disease and as a serological biomarker of disease severity. Methods: Forty-seven patients diagnosed as idiopathic PD according to diagnostic criteria of the UK Parkinson Disease Society Brain Bank, and 47 healthy individuals were enrolled. All patients were on medical  treatment of PD and were evaluated by Unified Parkinson’s disease Rating Scale (UPDRS), and Modified Hoehn and Yahr staging scale(HY). Cognitive function was assessed using Montreal Cognitive Assessment Scale (MOCA). TIPE2 serum level was measured in all participants. Results: PD patients had significantly higher levels of TIPE2 (P-value <0.001). Also, PD patients with cognitive impairment had significantly higher levels of TIPE2 (P-value= 0.039). TIPE2 level was positively correlated with score of modified HY staging (p-value o.oo1). Also,TIPE2 level was positively correlated with bradykinesia, total motor sub scores of UPDRS and total score of UPDRS (p-value 0.009, 0.019, 0.027 respectively). There was a significant negative correlation between TIPE2 and the scores of executives and visuospatial functions, attention, abstraction and total score of MoCA. Conclusions: TIPE2 serum levels in PD patients are higher than its serum level in healthy controls. Such high level of TIPE2 has a considerable impact on disease severity.

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References

  1. Kalia LV, Kalia SK, Lang AE. Disease‐modifying strategies for Parkinson's disease. Movement Disorders. 2015 Sep 15;30(11):1442-50.
  2. Hilker R, Portman AT, Voges J, Staal M, Burghaus L, Van Laar T, et al. Disease progression continues in patients with advanced Parkinson's Disease and effective subthalamic nucleus stimulation. Journal of Neurology and Neurosurgery Psychiatry. 2005;76 (9):1217-1221.
  3. .Gerhard A, Watts J, Trender‐Gerhard I, Turkheimer F, Banati RB, Bhatia K, et al. In vivo imaging of microglial activation with [11C] (R)‐PK11195 PET in corticobasal degeneration. Movement disorders: Official Journal of the Movement Disorder Society. 2004 Oct;19(10):1221-6.
  4. Sun H, Zhuang G, Chai L, Wang Z, Johnson D, Ma Y, et al. TIPE2 controls innate immunity to RNA by targeting the phosphatidylinositol 3-kinase–Rac pathway. The Journal of Immunology. 2012 Sep 15;189(6):2768-73.
  5. Wang Z, Fayngerts S, Wang P, Sun H, Johnson DS, Ruan Q,et al. TIPE2 protein serves as a negative regulator of phagocytosis and oxidative burst during infection. Proceedings of the National Academy of Sciences. 2012 Sep 18;109(38):15413-8.
  6. Hughes A, Ben-Shlomo Y, Daniel S, Lees A. What features improve the accuracy of clinical diagnosis in Parkinson’s disease: a clinicopathologic study. 1992; 42(6):1142 1146.
  7. Goetz C, Poewe W, Rascol O, Sampaio C, Stebbins GT, Counsell C, et al. Movement Disorder Society Task Force on Rating Scales for Parkinson's Disease. Movement Disorder. 2004 Sep; 19(9):1020-8.
  8. Movement Disorder Society Task Force on Rating Scales for Parkinson's Disease. The unified Parkinson's disease rating scale (UPDRS): status and recommendations. Movement Disorders. 2003 Jul;18(7):738-5o.
  9. Nasreddine ZS, Phillips NA, Bédirian V, Charbonneau S, Whitehead V, Collin I,et al. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. Journal of the American Geriatrics Society. 2005 Apr;53(4):695-9.
  10. Kouchaki E, Kakhaki RD, Tamtaji OR, Dadgostar E, Behnam M, Zaribaf A,et al. Correlation of serum levels and gene expression of tumor necrosis factor-α-induced protein-8 like-2 with Parkinson disease severity. Metabolic brain disease. 2018 Dec;33(6):1955-9.
  11. Cao X, Zhang L, Shi Y, Sun Y, Dai S, Guo C,et al. Human tumor necrosis factor (TNF)-alpha-induced protein 8-like 2 suppresses hepatocellular carcinoma metastasis through inhibiting Rac1. Molecular cancer. 2013 Dec;12(1):1-o.
  12. Zhang G, Zhang W, Lou Y, Xi W, Cui J, Geng M,et al. TIPE2 deficiency accelerates neointima formation by downregulating smooth muscle cell differentiation. Cell cycle. 2013 Feb 1;12(3):5o1-1o.
  13. Cereda E, Barichella M, Cassani E, Caccialanza R, Pezzoli G. Clinical features of Parkinson disease when onset of diabetes came first: a case-control study. Neurology. 2012 May 8;78(19):1507-11.
  14. Cholerton B, Johnson CO, Fish B, Quinn JF, Chung KA, Peterson-Hiller AL, et al. Sex differences in progression to mild cognitive impairment and dementia in Parkinson's disease. Parkinsonism & related disorders. 2018 May 1;5o:29-36.
  15. Gao L, Nie K, Tang H, Wang L, Zhao J, Gan R, et al. Sex differences in cognition among Chinese people with Parkinson’s disease. Journal of Clinical Neuroscience. 2015 Mar 1;22(3):488-92.
  16. Gennatas ED, Avants BB, Wolf DH, Satterthwaite TD, Ruparel K, Ciric R, et al. Age-related effects and sex differences in gray matter density, volume, mass, and cortical thickness from childhood to young adulthood. Journal of Neuroscience. 2017 May 17;37(20):5065-73.
  17. Zhang L, Shi Y, Wang Y, Zhu F, Wang Q, Ma C,et al. The unique expression profile of human TIPE2 suggests new functions beyond its role in immune regulation. Molecular immunology. 2011 May 1;48(9-10):1209-1

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